This proposal requests partial support for a 400 MHz high resolution nuclear magnetic resonance spectrometer. The hospital and NMR program will provide the additional funding and long-term support for this instrument. As part of the MGH NMR program, the spectrometer will be a resource to a community of PHS-supported biomedical researchers at the MGH and managed by the Internal Advisory Committee as outlined by the Division of Research Resources in the program announcement. The scope of the MGH NMR program, which is largely funded through PHS grants, has expanded to include in-vivo spectroscopy as well as sophisticated studies of chemical structure. Accordingly these experiments require high resolution equipment that does not presently exist at the MGH. Instruments with some of the capabilities required for the projects described herein are occasionally made available at neighboring institutions, but not for sufficient periods of time, and usually lack such support features as animal care facilities. The group of biomedical research projects this instrument will support is probably among the most wide ranging of sites receiving regular PHS funding. Projects include: metabolic studies of experimental cataract formation; ionic mechanisms regulating brain intracellular pH and high energy phosphates; metal chelates as NMR imaging contrast agents; proton spectroscopy and chemical shift imaging of lactate in tissue; proton, carbon, phosphorus and sodium spectroscopy of perfused hearts, and in-vivo hearts, using surgically implanted coils; novel high speed spectral analysis algorithms to to improve two-dimensional spectroscopy and spectroscopic imaging; high resolution solid state spectroscopy and spectroscopic imaging of bone and synthetic biomaterials; and measurement of solution conformation of proteins and synthetic peptides and genetically engineered proteins. It is anticipated that the level of scientific activities of PHS-supported researchers will be significantly enhanced by the presence of this instrument at the MGH.